The contribution of structural lipids to the permeability and lysis of lysosomes continues to be studied. Lysophospholipids and free fatty acids are significantly elevated during lysis of hepatic lysosomes. The relevance of this observation to acidosis and infarction of the myocardium is being pursued. Significant release of acid hydrolases after one hour of ischemia of the myocardium has been demonstrated in our laboratory in the endocardium of a canine model of infarction. The mechanism of release of lysosomal enzymes, as well as interventions to regard it, are under investigation. The sarcolemma and sarcoplasmic reticulum may be impaired in heart failure in the myopathic hamster and in skeletal muscle of the dystrophic chicken. The application of zonal centrifugation to both conditions in our laboratory has shown marked cross-contamination of the sarcoplasmic reticulum of dystrophic tissue by several organelles. This contamination appears to contribute to the impairment of the uptake of calcium by the dystrophic sarcoplasmic reticulum, which may prove to function normally upon removal of contamination. We are attempting purification of myocardial sarcolemma to assess the function of lipid-dependent enzymes during failure and infarction.